Opto-electrical device and method for artifact reduction

ABSTRACT

An optical electrode having a plurality of electrodes, including a recording electrode having a roughened surface and an optical light source configured to emit light, wherein at least a portion of the light impinges on the recording electrode. Also disclosed are methods of producing an optical electrode and an opto-electronic neural interface system.

PRIORITY DATA

This application is a continuation of U.S. patent application Ser. No.15/728,251, filed Oct. 9, 2017, which is a continuation of U.S. patentapplication Ser. No. 13/557,516, filed Jul. 25, 2012, now U.S. Pat. No.9,782,091, which claims benefit of U.S. Provisional Application No.61/511,358 filed Jul. 25, 2011, the disclosures of each are incorporatedherein by reference in their entirety as if fully set forth below andfor all applicable purposes.

FEDERALLY SPONSORED RESEARCH

This invention was made with government support under 1R43NS073185-01awarded by National Institutes of Health, National Institute ofNeurological Disorders and Stroke. The government has certain rights inthe invention.

TECHNICAL FIELD

This invention relates generally to the neural device field, and morespecifically to an improved opto-electrical device with artifactreduction in the neural device field.

BACKGROUND

One recent advance in neuroscience is the use of optogenetic tools toperturb neural circuits, particularly neural circuits with cell-typespecificity. These optogenetic tools enable optical stimulation ofneurons using light-sensitive ion channels (such as transfectionoccurring from viral vectors carrying opsins such as ChR2 orHalorhodopsin) for optical stimulation and neuromodulation applications.For example, a transfected neuron may be selectively activated orsilenced as a result of exposure to a certain wavelength of light.Optogenetics allows experimenters or medical practitioners to use lightstimulation to selectively excite neural channels and/or inhibit otherneural channels with high precision.

However, in devices where neural sensing is combined with neural opticalstimulation, the neural sensing elements experience increased noise andartifact from the photoelectrochemical (PEC) effect, also known as theBecquerel effect. The PEC effect results in artifacts of electricalsignals that interfere with or obscure the recording of desired neuralelectrical signals, thereby interfering with the function and operationof neural optogenetic devices. Thus, there is a need in the neuraldevice field to create an improved opto-electrical device with artifactreduction. This invention provides such an improved opto-electricaldevice.

SUMMARY

In one embodiment, the invention provides an optical electrode having aplurality of electrodes, including a recording electrode having aroughened surface and an optical light source configured to emit light,wherein at least a portion of the light impinges on the recordingelectrode.

In another embodiment, the invention provides a method of producing anoptical electrode with a reduced photoelectrochemical artifact. Themethod includes steps of coupling a plurality of electrodes to acarrier, the plurality of electrodes having at least one recordingelectrode; providing a roughened surface on the at least one recordingelectrode; and coupling an optical light source to the carrier, theoptical light source being configured to emit light and wherein at leasta portion of the light impinges on the at least one recording electrode.

In yet another embodiment, the invention provides an opto-electronicneural interface system. The system includes an optical electrode havinga plurality of electrodes, including a recording electrode having aroughened surface, and an optical light source configured to emit light,wherein at least a portion of the light impinges on the recordingelectrode; an electrical subsystem in communication with the pluralityof electrodes; and an optical subsystem in communication with theoptical light source.

Other aspects of the invention will become apparent by consideration ofthe detailed description and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side-view schematic of one embodiment of an opticalelectrode.

FIG. 2 is a perspective view schematic of another embodiment of anoptical electrode.

FIG. 3 is a sectional view of an embodiment of an electrode withroughening material applied to the electrode surface.

FIG. 4 is a sectional view of another embodiment of a roughenedelectrode.

FIGS. 5A and 5B show electrical recordings from electrodes depicting theartifact stabilization time for electrodes that are smooth (uncoated;FIG. 5A) or roughened (treated with PEDOT at 3 nC/μm²; FIG. 5B).

FIGS. 6A and 6B show electrical recordings from electrodes depicting theartifact dissipation time for electrodes that are smooth (uncoated; FIG.6A) or roughened (treated with PEDOT at 1 nC/μm²; FIG. 6B).

FIG. 7 shows the level of photoelectrochemical artifact on a series ofrecording electrodes in which only the even-numbered electrodes areroughened, using 473 nm light applied parallel to the probe shank.

FIG. 8 shows the level of photoelectrochemical artifact on a series ofrecording electrodes in which only the even-numbered electrodes areroughened, using 635 nm light applied parallel to the probe shank.

FIG. 9 shows the level of photoelectrochemical artifact on a series ofrecording electrodes in which only the even-numbered electrodes areroughened, using 473 nm light applied perpendicular to the probe shank.

FIG. 10 shows the level of photoelectrochemical artifact on a series ofrecording electrodes in which only the even-numbered electrodes areroughened, using 473 nm light applied parallel to the probe shank and ata distance of 200 μm from the leftmost electrode.

FIG. 11 shows a bar graph depicting the average photoelectrochemicalartifact amplitude from FIG. 10 of the roughened and unroughenedelectrodes.

FIG. 12 shows an embodiment of a system for use with embodiments of thedisclosed optical electrode.

DETAILED DESCRIPTION

Before embodiments of the invention are explained in detail, it is to beunderstood that the invention is not limited in its application to thedetails of construction and the arrangement of components set forth inthe following description or illustrated in the following drawings. Theinvention is capable of other embodiments and of being practiced or ofbeing carried out in various ways.

As shown in FIGS. 1 and 2, an opto-electrical device 100, or “optrode”or “optical electrode,” according to one embodiment includes: a carrier110 insertable in tissue; an electrode array 112 disposed on the carrier110 and having a plurality of electrodes including at least onerecording electrode site having a roughened surface 112 a, the recordingelectrode configured to ‘record’ or sense electrical signals from itssurroundings; and an optical light source 120 configured to illuminateselectively-targeted regions of the tissue. The opto-electrical device100 may be used in applications with optogenetic techniques involvingoptical stimulation patterns of tissue and neural recordingcapabilities. In various embodiments, the opto-electrical device 100 isinsertable or implantable in neural tissue (e.g. the brain), but mayadditionally and/or alternatively be used with other suitable tissues.

The carrier 110 functions to provide structural support for theelectrode array 112 and, in some cases, for insertion and/orimplantation of the opto-electrical device 100 into tissue. The carrier110 may be planar, cylindrical, or other suitable shapes. In someembodiments, the carrier 110 may be similar to that in the neural devicedescribed in U.S. Patent Application number 2011/0112591 (hereinafterreferred to as the '591 publication) entitled “Waveguide neuralinterface device,” which is incorporated in its entirety by thisreference. However, other suitable carriers 110 may be used. The carrier110 may be made of other suitable materials or combination of materials,including those listed in the '591 publication or in US 2011/0093052(hereinafter referred to as the '052 publication) entitled “NeuralInterface System,” which is incorporated in its entirety by thisreference. In some embodiments, the waveguide 120 may serve as a carrierwith an electrode array 112 being associated with the waveguide 120. Invarious embodiments, optrodes such as those disclosed herein may be usedwith a neural interface system, such as disclosed in the '052publication.

In certain embodiments the opto-electrical device 100 is part of aneural interface system 1000, which may include an electrical subsystem1100, an optical subsystem 1200, and a controller 2000. The electricalsubsystem 1100 functions to operate with the electrode array 112, forexample when the electrode array 112 is implanted into a subject 1500(FIG. 13). The subject 1500 may include any number of animals into whichthe opto-electrical device 100 may be implanted and with which theneural interface system 1000 may be employed, including withoutlimitation rodents (e.g. rats, mice, rabbits, etc.) and primates (e.g.humans, monkeys, etc.).

The controller 2000 may control one or both of the electrical subsystem1100 and the optical subsystem 1200 to carry out the functions of theneural interface system 1000 such as those disclosed herein. Theelectrical subsystem 1100, optical subsystem 1200, and controller 2000may be integrated into a single unit or may be separate units, and eachmay be external to the subject 1500 or may be part of an implanteddevice. Each of the electrical subsystem 1100, optical subsystem 1200,and controller 2000 may include a processor, memory, storage,amplifiers, A/D convertors, input/output mechanisms, and communicationmechanisms, including capabilities for wired and/or wirelesscommunications within the components of the system 1000 and between thesystem 1000 and external computers and networks.

The electrical subsystem 1100 includes at least one of severalvariations of suitable electronic subsystems to operate with (e.g. senseelectrical signals at) the electrode array 112 or combinations thereof.The electrical subsystem 1100 may be a printed circuit board with orwithout onboard amplifier or integrated circuits and/or on-chipcircuitry for signal sensing and/or conditioning and/or stimulusgeneration, an Application Specific Integrated Circuit (ASIC), amultiplexer chip, a buffer amplifier, an electronics interface, a pulsegenerator (which produces signals such as a high-frequency, pulsedelectric current, and which in certain embodiments may be implantable),a power supply (which in various embodiments can include an implantablerechargeable battery), integrated electronics for signal processing ofthe input (recorded) or output (stimulation) signals (either of whichmay be processed in real time), other suitable electrical subsystem, orcombinations thereof, as disclosed in the '052 publication.

The optical subsystem 1200, which is in communication with the opticallight source 120, includes power and control units to control the lightsource 120 in order to generate light pulses of suitable wavelength,duration, intensity, and pulse shape. The optical light source 120functions to illuminate surrounding tissue and stimulating targetedtissue. In some embodiments, the optical light source 120 is coupled tothe carrier such that the light from the optical light source 120 has anangle of incidence that is minimal relative to the surface of therecording electrode sites (e.g. less than normal incidence). In oneembodiment, the optical light source 120 provides illuminationapproximately parallel to the surface of the recording electrode site.However, the optical light source 120 may be positioned in othersuitable locations relative to the electrode site surface.

In various embodiments, the optical light source 120 may include one ormore LEDs or a waveguide, where the LEDs may be included on the carrier110 (e.g. in the vicinity of the electrode array 112). Alternatively,the waveguide may be coupled to a light source that is nearby (e.g. partof the implantable device) or remote (e.g. part of an external componentassociated with the implantable device). The light source to which thewaveguide is coupled may be one or more LEDs, a laser, or other suitablelight source (e.g. as disclosed in the '591 publication), and in variousembodiments is controlled by the optical subsystem 1200. The opticallight source 120 can have a number of configurations relative to theelectrode array 112, e.g. as shown in the '591 publication, and as aresult light emitted from the optical light source 120 may impinge onone or more electrodes in the electrode array 112 in a direction that isparallel, perpendicular, or at other angles relative to the surface onwhich the plurality of electrodes is disposed.

The electrode array 112 functions to electrically communicate with itssurroundings. In various embodiments, the electrode array 112 caninclude one or more recording electrode sites that sense and recordneural signals in surrounding tissue, and in some embodiments theelectrode array 112 may additionally and/or alternatively includestimulation electrode sites. The electrode array 112 may be arrangedlongitudinally along (e.g. as shown in FIGS. 1 and 2) and/orcircumferentially around a cylindrical carrier 110, along a face or edgeof a planar carrier 110, or in other suitable arrangements on thecarrier 110. The opto-electrical device 100 may further include anoptical light source 120 such as a waveguide arranged proximate to theelectrode array 112, as shown in FIGS. 1 and 2 or as shown and describedin the '591 publication. In various embodiments, the electrode sites mayinclude conductive metal (e.g. gold, platinum, iridium,platinum-iridium, titanium nitride, iridium oxide, etc.) and may beformed by microfabrication techniques, such as thin-film or othermicroelectromechanical systems (MEMS) manufacturing processes.

A metal electrode that is “smooth” (not roughened) in general has anaverage roughness (R_(a)) of less than 10 nm (average of series ofmaximum and minimum height measurements). It is demonstrated herein thattreatments that increase the average roughness of a recording electrode(or a material applied thereto, FIG. 3) to greater than about 10 nm havethe effect of reducing the photoelectrochemical artifact. According tovarious embodiments, a roughened electrode 112 a has an averageroughness of greater than 10 nm, greater than 20 nm, greater than 30 nm,greater than 50 nm, or greater than 100 nm. Average roughness (R_(a)) isan arithmetic average of absolute values of vertical deviations ofheight on a surface, expressed in units of height (e.g. nanometers).

In various embodiments, one or more recording electrodes 112 a in theelectrode array 112 may have a roughened surface (FIGS. 1, 3, and 4).The roughening can take a number of forms and may produce a tortuoussurface such as with recesses, pores, and/or other surface modificationsthat reduce the smoothness and increase the effective surface area ofthe electrode surface. The roughened surface may have a pattern (e.g.grooves, cross-hatching, regularly-spaced protrusions or depressions,etc.) or may be essentially random. The roughened surface 112 a may beproduced by applying a material (FIG. 3) to the electrode, by producingan electrode having a roughened surface as part of the electrode itself(FIG. 4), or a combination of methods. The material applied to thesurface can include PEDOT/PSS(poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate), iridiumoxide, or nanostructures (e.g. nanotubes, nanoparticles, nanospheres)made from a variety of materials. For example, glass or polystyrenenanospheres or microspheres may be applied to one or more electrodes onthe electrode array 112 during microfabrication to form a highly densepattern on the modified electrode array. In some embodiments, platinummay be applied to a surface using electrodeposition of Pt nanoparticles.In certain embodiments, the recording electrode and the roughenedsurface 112 a may be substantially free of transparent andsemi-transparent conductors such as indium-tin-oxide.

In one embodiment, polystyrene nanospheres were applied to an electrodesurface producing feature sizes of at least 200 nm in height and anaverage roughness R_(a) of 300 nm. In one particular embodiment in which800 nm nanospheres were applied, R_(a) was found to be 365±37 nm(average±standard error) and the RMS (root mean square) surfaceroughness was 368 nm. In various embodiments, a roughened electrode 112has an RMS surface roughness of greater than 50 nm, greater than 100 nm,or greater than 200 nm.

In another embodiment, PEDOT/PSS was applied to a micromachinedelectrode (e.g. using techniques such as those in U.S. Pat. No.8,005,526, which incorporated herein by reference) and the size offeatures was found to range from 50 nm-1000 nm and the R_(a) was 700±243nm for particular surfaces that were measured.

In still other embodiments iridium oxide can be applied to the recordingelectrode to roughen the surface, as shown in Dias et al. (2010, “Newdry electrodes based on iridium oxide (IrO) for non-invasivebiopotential recordings and stimulation,” Sensors and Actuators A:Physical, 164:28-34; incorporated by reference herein). Iridium oxidecan produce filamentous, globular, or other surface features withfeature sizes of 10 nm or greater and average roughness R_(a) valuesranging from 27 nm to 183 nm.

According to further embodiments, the electrode surface may be roughenedin one or more variations of surface modification steps. The electrodemodification may include direct metal deposition (e.g., physical vapordeposition or PVD, sputtering, evaporation), electrochemical depositionfrom a solution, electrochemical activation (e.g. oxide growth), asol-gel process, and/or micromachining and microfabrication techniquesincluding the use of plasma etching (in which the exact chemistrydepends on the type of metal in the electrode surface). Variousparameters, such as duration, pressure, and temperature of depositionand other tools may also be adjusted to selectively modify the electrodesite surfaces. However, other suitable methods of selectivelydepositing, forming, or machining a rough, tortuously texturedconductive medium may be used. The electrode surface may be modified bymicromachining or other suitable techniques to create a porous,discontinuous surface with a similarly tortuous electrical double layer.Furthermore, the electrode site surfaces may include materials that arenaturally recessed and/or porous.

Each of the one or more roughened electrodes 112 a, which are generallyplanar, has a geometric surface area based on its physical dimensionssuch as length, width, and/or diameter. On the other hand, each of theone or more roughened electrodes 112 a has an effective surface areathat is at least two to ten times greater than the geometric surfacearea of the same electrode, and in various embodiments is at leasttwenty, fifty, one hundred, or one thousand times greater than thegeometric surface area of the same electrode.

When a roughened electrode surface is immersed in brain tissue or otherelectrolyte environments and subsequently exposed to light, theroughening reduces the electrical artifacts that occur due to thephotoelectrochemical effect (also known as the Becquerel effect). Asmentioned above, these electrical artifacts, which occur with use ofconventional optrodes, may interfere with or obscure the recording ofthe desired neural signals. In one hypothesis, the photoelectrochemicaleffect is thought to begin with a photoelectric event in which photonscause emission of electrons upon striking a non-transparent metalsurface. Many of these emitted electrons are thought to enter thesurrounding environment, where they directly or indirectly interact withand disturb the electrical double layer (a double layer of charge thatspontaneously forms at the interface between the electrode andsurrounding electrolyte solution). According to this hypothesis, whenmany emitted electrons simultaneously interfere with the electricaldouble layer in a particular region, the synchronized interferences maybe observed as an artifact of voltage fluctuation measured by anelectronic amplifier connected to the electrode.

Without being limited by theory, the roughening may reduce the artifactdue to the photoelectrochemical effect by increasing an effectivesurface area of the electrode and producing a lower surface chargedensity. The lower surface charge density may reduce the probabilitythat an emitted electron will interact with a charge in the electricaldouble layer.

The following are examples in which it is demonstrated that roughening arecording electrode reduces the photoelectrochemical artifact thatoccurs when the electrode is placed in an electrolyte solution.

In one example, two groups of electrode sites were placed in an ionicsolution of PBS IX and electrical signals were recorded after beingimpinged with a laser diode: a first group in which the electrode siteswere coated with PEDOT at 3 nC/μm² (FIG. 5B) or at 1 nC/μm² (FIG. 6B),and a second group in which the electrode sites were not substantiallycoated with PEDOT, such that the first group of electrode sites (FIGS.5B, 6B) had surfaces substantially roughened compared to that of thesecond group of electrode sites (FIGS. 5A, 6A). As shown in FIGS. 5A and5B, the signal from the roughened electrode sites (using nanospherepatterning) recorded significantly shorter artifact stabilization timethan the unroughened electrode sites. As shown in FIGS. 6A and 6B, thesignal from the roughened electrode sites recorded an artifactsignificantly smaller in amplitude than that from the unroughenedelectrode sites. Furthermore, after removal of the light source, in thesignal from the roughened electrode sites the artifact dissipated as aninverted waveform, more quickly than in the signal from the unroughenedelectrode sites. Electrophysiologists may also easily filter outshort-duration artifacts more readily than artifacts having apulse-width similar to the physiological signal, e.g. the pulse-width ofa single-cell action potentials.

In another example, a smaller electrode having a smaller recessedsurface area (˜177 m²) and a larger electrode having a larger recessedsurface area (˜703 μm²) were placed in an ionic solution and illuminatedwith light incident approximately parallel to the electrode surface.Comparison of the signal recorded by the smaller electrode and thesignal recorded by the larger electrode suggested that when light isincident on an electrode approximately parallel to the surface, then thesurface area of the electrode is inversely proportional to the amplitudeof the artifact.

In still another example, the even-numbered electrodes in a lineararray, consisting of platinum, were patterned with nanoscale platinumstructures to roughen the surface of even-numbered sites (FIG. 7). Light(473 nm, SO Hz, S ms, 1 mW) was applied parallel to the probe shankcontaining the linear array, closest to electrode number 1. As shown inFIG. 7, the level of artifact on the even-numbered electrodes (onlyvalues for electrodes 2, 6, and 12 are shown) is greatly reducedcompared to the uncoated electrodes. For electrode 2 the artifact isreduced by 90% compared to the predicted level of artifact for thatelectrode after accounting for spreading and scattering (FIG. 7, inset).Similar results were obtained when the electrode was illuminated undersimilar conditions but with 63S nm light (FIG. 8). In this case, theartifact for electrode 2 was reduced by 78% compared to the modeledcorrection for scattering and spreading (FIG. 8, inset).

In yet another example, an optical electrode in which the even-numberedelectrodes were roughened was illuminated with light (473 nm, 50 Hz, 5ms, 2 mW) perpendicular to the shank of the electrode with the lightsource being essentially adjacent to the electrodes (d≈0; FIG. 9). Theroughened even-numbered electrodes showed a 29% decrease in artifact onaverage compared to the uncoated (smooth) odd-numbered electrodes.

FIG. 10 shows the artifact amplitude for an optical electrode with alinear array of recording electrodes in which the even-numberedrecording electrodes are roughened. Light (473 nm, 50 Hz, 5 ms, 2 mW) isapplied parallel to the shank of the optical electrode using an opticalfiber placed at approximately 200 μm from the proximal recordingelectrode (i.e. 200 μm to the left of electrode 12 in the diagram ofFIG. 10). Under these conditions, there is an average of 57.5% reductionin the photoelectrochemical artifact observed with the roughenedrecording electrodes compared to the unroughened/uncoated (smooth)electrodes (FIG. 11).

Thus, the invention provides, among other things, an optical electrodeand a method of producing an optical electrode. Various features andadvantages of the invention are set forth in the following claims.

The invention claimed is:
 1. An apparatus, comprising: a carrier; anelectrode disposed on the carrier, wherein the electrode is configuredto sense and record neural signals in a body tissue, and wherein theelectrode has a roughened surface; and a light source disposed on thecarrier, wherein the light source is configured to emit light toilluminate at least a portion of the body tissue, wherein at least aportion of the light is directed at the roughened surface of theelectrode.
 2. The apparatus of claim 1, further including a plurality ofadditional electrodes, wherein at least one of the additional electrodesis a stimulation electrode configured to provide electrical stimulationto the body tissue.
 3. The apparatus of claim 2, wherein: the electrodeand the additional electrodes are arranged in an array that extends in alongitudinal direction; and the light source is aligned with the arrayin the longitudinal direction.
 4. The apparatus of claim 2, wherein: thecarrier has a cylindrical shape; and the electrode and the additionalelectrodes are disposed circumferentially around the carrier.
 5. Theapparatus of claim 2, wherein at least one of the additional electrodesis a recording electrode having an unroughened surface.
 6. The apparatusof claim 1, wherein the light source provides illumination that isparallel to a surface of the carrier on which the electrode is disposed.7. The apparatus of claim 1, wherein the roughened surface has anaverage roughness greater than 10 nanometers.
 8. The apparatus of claim1, wherein the roughened surface includes recesses or pores.
 9. Theapparatus of claim 8, wherein the recesses or pores are randomlydistributed.
 10. The apparatus of claim 1, wherein the roughened surfaceincludes patterned grooves, cross-hatchings, protrusions, ordepressions.
 11. The apparatus of claim 1, wherein the roughened surfaceis substantially free of transparent or semi-transparent conductors. 12.An apparatus, comprising: a carrier; a recording electrode and astimulation electrode each disposed on the carrier, wherein therecording electrode is configured to sense and record neural signals ina body tissue, wherein the stimulation electrode is configured toprovide electrical stimulation to the body tissue, wherein the recordingelectrode comprises a roughened external material having a back sideattached to an electrically conductive material to thereby provide therecording electrode with a roughened surface forming a front side of theroughened external material, and wherein the roughened surface has anaverage roughness greater than 10 nanometers; and a light sourcedisposed on the carrier, wherein the light source is configured toilluminate at least a portion of the body tissue and the roughenedsurface of the recording electrode.
 13. The apparatus of claim 12,wherein the roughened surface includes: a plurality of randomlydistributed recesses or pores; or a plurality of periodicallydistributed grooves, cross-hatchings, protrusions, or depressions.